Zerumbone mediated CD1d inhibition suppresses epithelial to mesenchymal transition in triple negative breast cancer.

In vitro study using TNBC cell lines, molecular docking, MD simulations, and TCGA cohort analysis

“This study examines the effect of CD1d inhibition on EMT in TNBC.”

MDA-MB-468 and MDA-MB-231 triple-negative breast cancer cell lines and TCGA-BRCA patient data

“We demonstrate that Zerumbone (ZER, 20 µM), a phytochemical, downregulates CD1d, reducing EMT markers, cell migration, and adhesion in MDA-MB-468 and MDA-MB-231 TNBC cell lines.”

n = 1226 patient samples for TCGA analysis; in vitro experiments performed in triplicate

“TCGA BRCA RNA-seq patient data were procured from UCSC Xena with STAR-FPKM (n = 1226).”

In vitro treatments assessed at 24 hours; MD simulations run for 100 nanoseconds

“All studies were conducted up to 100 nanoseconds (ns) of runtime.”

Zerumbone downregulates CD1d, reducing EMT markers, cell migration, and adhesion

“We demonstrate that Zerumbone (ZER, 20 µM), a phytochemical, downregulates CD1d, reducing EMT markers, cell migration, and adhesion in MDA-MB-468 and MDA-MB-231 TNBC cell lines.”

CD1d upregulation by AGC and TA promotes EMT, enhances migration and adhesion

“Conversely, CD1d upregulation by α-galactosylceramide (AGC, 2 µM) and thymosin α-1 (TA, 2 µM) promotes EMT, enhances migration and adhesion.”

High CD1D expression correlates with EMT signature and reduced overall survival in TNBC patients

“Further grouping the TNBC into CD1D-high and CD1D-low revealed a significant reduction in overall survival among patients with high CD1D expression (log-rank p = 3.53e-02).”

Experiments limited to two in vitro cell lines, lack of animal studies, and reliance on in silico methods for direct physical interaction confirmation

“All the experiments conducted were primarily in vitro models limited to two TNBC cell lines, which may not completely represent all TNBC cells.”